Detection of endogenous levels of N-acetyltryptamine, a mixed melatonin agonist/antagonist, in human and rhesus macaque plasma

N-Acetyltryptamine is a melatonin (5-methoxy N-acetyltryptamine) receptor mixed agonist/antagonist. A liquid chromatography/tandem mass spectrometric method was developed to quantitate endogenous levels of N-acetyltryptamine and melatonin in plasma. Using this assay, N-acetyltryptamine was detected in daytime plasma from human volunteers, rhesus macaques, and rats. In daytime human plasma, concentrations of N-acetyltryptamine ranged from 0.01 to 0.25 nM, while melatonin concentrations ranged from 0.01 to 0.4 nM. Twenty-four hour studies of rhesus macaque plasma revealed that N-acetyltryptamine increases up to 6-fold at night, to concentrations that exceed those of melatonin by ~10-fold. This is the first report on the endogenous levels of N-acetyltryptamine in circulation. The levels of N-acetyltryptamine observed in circulation supports the hypothesis that this compound may play a physiological role as an endocrine or paracrine chonobiotic, though actions mediated by the melatonin receptor.